Analysis of the role of TGF-b family and Smad signaling in musculoskeletal regulation
Project/Area Number |
24592278
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Saitama Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Takenobu 埼玉医科大学, 医学部, 教授 (80245802)
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Co-Investigator(Renkei-kenkyūsha) |
OHTE Satoshi 埼玉医科大学, 医学部, 助教 (00547979)
SASANUMA Hiroki 埼玉医科大学, 医学部, 研究員 (30571707)
MIYAMOTO Arei 埼玉医科大学, 医学部, 研究員 (70634591)
OSAWA Kenji 埼玉医科大学, 医学部, 助教 (70638238)
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Research Collaborator |
TSUKAMOTO Sho 埼玉医科大学, 医学部 (20707658)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | 転写因子 / 細胞内伝達情報 / 分化 / 骨格筋 / 運動器 / 細胞内情報伝達 |
Outline of Final Research Achievements |
Transforming Growth Factor-β (TGF-β) family cytokines play crucial role for musculoskeletal development, regeneration and homeostasis. To clarify the molecular mechanisms of TGF-β family, we developed a mouse line carrying skeletal muscle-specific knockout of Smad4, which is an essential transcriptional factor for intracellular signaling of TGF-β family. Because the muscle-specific Smad4 KO mice were lethal, we prepared mononuclear cells from the skeletal muscle tissue of the Smad4 floxed mice and cultured them in vitro. A deletion of Smad4 in the cells by expression of Cre DNA recombinase in vitro stimulated differentiation into myocytes and myotubes, suggesting that Smad4 represses myogenesis in myoblasts. These findings suggest that the Smad4-dependent intracellular signaling of the TGF-β family plays an important role during skeletal muscle development. These findings may provide new therapeutic strategies for diseases caused by dysregulation of the TGF-β family signaling.
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling.2014
Author(s)
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Machiya A, Jimi E, Kokabu S, Katagiri T.
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Journal Title
Scientific Reports
Volume: 4
Issue: 1
Pages: 7596-7596
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Establishment of a novel model of chondrogenesis using murine embryonic stem cells carrying fibrodysplasia ossificans progressiva-associated mutant ALK2.2014
Author(s)
Fujimoto M, Ohte S, Shin M, Yoneyama K, Osawa K, Miyamoto A, Tsukamoto S, Mizuta T, Kokabu S, Machiya A, Okuda A, Suda N, Katagiri T.
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Journal Title
Biochmical and Biophysical Research Communications
Volume: 455
Issue: 3-4
Pages: 347-352
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes.2013
Author(s)
Shin M, Ohte S, Fukuda T, Sasanuma H, Yoneyama K, Kokabu S, Miyamoto A. Tsukamoto S, Hohjoh H, Jimi E, Katagiri T.
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Journal Title
J Bone Miner Metab.
Volume: 31
Issue: 1
Pages: 34-43
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Trichocyalides A and B, new inhibitors of alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblasts, produced by Trichoderma sp. FKI-55132012
Author(s)
Fukuda T, Uchida R, Ohte S, Inoue H, Yamazaki H, Matsuda D, Nonaka K, Masuma R, Katagiri T, Tomoda H.
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Journal Title
The Journal of antibiotics (Tokyo)
Volume: 65
Issue: 11
Pages: 565-569
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Smad9 is a new type of transcriptional repressor in BMP signaling.2014
Author(s)
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Jimi E, Kokabu S, Katagiri T.
Organizer
The 12th RCGM International Symposium of Academic Frontier
Place of Presentation
埼玉医科大学30周年記念講堂(埼玉県日高市)
Year and Date
2014-10-31 – 2014-11-01
Related Report
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[Presentation] Chondrogenic differentiation of murine embryonic stem cells carrying an active form of ALK2.2014
Author(s)
Fujimoto M, Ohte S, Shin M, Yoneyama K, Mizuta T, Osawa K, Tsukamoto S, Miyamoto A, Okuda A, Suda N, Katagiri T.
Organizer
The 12th RCGM International Symposium of Academic Frontier
Place of Presentation
埼玉医科大学30周年記念講堂(埼玉県日高市)
Year and Date
2014-10-31 – 2014-11-01
Related Report
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[Presentation] Smad8 is a novel regulator of BMP signaling.2014
Author(s)
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Jimi E, Kokabu S, Katagiri T.
Organizer
10th International BMP Conference
Place of Presentation
ベルリン(ドイツ)
Year and Date
2014-09-16 – 2014-09-20
Related Report
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[Presentation] Smad8 negatively regulates BMP signaling in a dominant negative fashion.2014
Author(s)
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Jimi E, Kokabu S, Katagiri T.
Organizer
2014 ASBMR Annual Meeting
Place of Presentation
ヒューストン(アメリカ)
Year and Date
2014-09-12 – 2014-09-15
Related Report
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[Presentation] Establishment and characterization of a novel Tet-Off embryonic stem cell lines carrying ALK2.2014
Author(s)
Fujimoto M, Ohte S, Shin M, Yoneyama K, Osawa K, Tsukamoto S, Miyamoto A, Mizuta T, Kokabu S, Okuda A, Suda N, Katagiri T.
Organizer
2014 ASBMR Annual Meeting
Place of Presentation
ヒューストン(アメリカ)
Year and Date
2014-09-12 – 2014-09-15
Related Report
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[Presentation] A novel regulation of BMP signaling by Smad8.2014
Author(s)
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Jimi E, Kokabu S, Katagiri T.
Organizer
FASEB Science Research Conferences Skeletal Muscle Satellite and Stem Cells
Place of Presentation
スティームボート・スプリングズ(アメリカ)
Year and Date
2014-07-20 – 2014-07-25
Related Report
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[Presentation] stablishment of a novel model for chondrogenic differentiation using murine embryonic stem cells carrying mutant ALK2.2014
Author(s)
Fujimoto M, Ohte S, Shin M, Yoneyama K, Osawa K, Tsukamoto S, Miyamoto A, Mizuta T, Kokabu S, Okuda A, Suda N, Katagiri T.
Organizer
FASEB Science Research Conferences Skeletal Muscle Satellite and Stem Cells
Place of Presentation
スティームボート・スプリングズ(アメリカ)
Year and Date
2014-07-20 – 2014-07-25
Related Report
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[Presentation] Identification of a Novel BMP-inducible Transcript, BIT-1, by Utilizing the Conserved BMP-Responsive Elements in the Id Genes2012
Author(s)
Masashi Shin, Satoshi Ohte, Toru Fukuda, Hiroki Sasanuma, Katsumi Yoneyama, Shoichiro Kokabu, Sho Tsukamoto, Hirohoko Hohjoh, Eijiro Jimi, Takenobu Katagiri
Organizer
2012 ASBMR Annual Meeting
Place of Presentation
ミネアポリス(アメリカ)
Related Report
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[Presentation] Smad8 is a Novel Type Regulator of BMP Signaling
Author(s)
Sho Tsukamoto, Satoshi Ohte, Mai Fujimoto, Takato Mizuta, Arei Miyamoto, Kenji Osawa, Shoichiro Kokabu, Eiko Murata, Eijiro Jimi, Takenobu Katagiri
Organizer
2013 ASBMR Symposium Cutting Edge Discoveries in Muscle Biology, Disease and Therapeutics
Place of Presentation
Baltimore Convention Center ( アメリカ )
Related Report
Invited